Initial Cluster Analysis

Overview

Journal J Comput Biol

Specialties Biology
Molecular Biology

Date 2017 Aug 4

PMID 28771374

Citations 4

Authors

Stephen F Altschul

Andrew F Neuwald

Affiliations

Soon will be listed here.

Abstract

We study a simple abstract problem motivated by a variety of applications in protein sequence analysis. Consider a string of 0s and 1s of length L, and containing D 1s. If we believe that some or all of the 1s may be clustered near the start of the sequence, which subset is the most significantly so clustered, and how significant is this clustering? We approach this question using the minimum description length principle and illustrate its application by analyzing residues that distinguish translational initiation and elongation factor guanosine triphosphatases (GTPases) from other P-loop GTPases. Within a structure of yeast elongation factor 1[Formula: see text], these residues form a significant cluster centered on a region implicated in guanine nucleotide exchange. Various biomedical questions may be cast as the abstract problem considered here.

Citing Articles

SPARC: Structural properties associated with residue constraints.

Neuwald A, Yang H, Nixon B Comput Struct Biotechnol J. 2022; 20:1702-1715.

PMID: 35495120 PMC: 9020082. DOI: 10.1016/j.csbj.2022.04.005.

Identifying Function Determining Residues in Neuroimmune Semaphorin 4A.

Chapoval S, Lee M, Lemmer A, Ajayi O, Qi X, Neuwald A Int J Mol Sci. 2022; 23(6).

PMID: 35328445 PMC: 8953949. DOI: 10.3390/ijms23063024.

Statistical investigations of protein residue direct couplings.

Neuwald A, Altschul S PLoS Comput Biol. 2019; 14(12):e1006237.

PMID: 30596639 PMC: 6329532. DOI: 10.1371/journal.pcbi.1006237.

Inferring joint sequence-structural determinants of protein functional specificity.

Neuwald A, Aravind L, Altschul S Elife. 2018; 7.

PMID: 29336305 PMC: 5770160. DOI: 10.7554/eLife.29880.

References

Neuwald A, Altschul S . Inference of Functionally-Relevant N-acetyltransferase Residues Based on Statistical Correlations. PLoS Comput Biol. 2016; 12(12):e1005294. PMC: 5225019. DOI: 10.1371/journal.pcbi.1005294. View

Fischer J, Mayer C, Soding J . Prediction of protein functional residues from sequence by probability density estimation. Bioinformatics. 2008; 24(5):613-20. DOI: 10.1093/bioinformatics/btm626. View

Karlin S, Zhu Z . Characterizations of diverse residue clusters in protein three-dimensional structures. Proc Natl Acad Sci U S A. 1996; 93(16):8344-9. PMC: 38673. DOI: 10.1073/pnas.93.16.8344. View

Leipe D, Wolf Y, Koonin E, Aravind L . Classification and evolution of P-loop GTPases and related ATPases. J Mol Biol. 2002; 317(1):41-72. DOI: 10.1006/jmbi.2001.5378. View

Jeffreys H . An invariant form for the prior probability in estimation problems. Proc R Soc Lond A Math Phys Sci. 2010; 186(1007):453-61. DOI: 10.1098/rspa.1946.0056. View

Neuwald A . A Bayesian sampler for optimization of protein domain hierarchies. J Comput Biol. 2014; 21(3):269-86. PMC: 3948484. DOI: 10.1089/cmb.2013.0099. View

Janda J, Busch M, Kuck F, Porfenenko M, Merkl R . CLIPS-1D: analysis of multiple sequence alignments to deduce for residue-positions a role in catalysis, ligand-binding, or protein structure. BMC Bioinformatics. 2012; 13:55. PMC: 3391178. DOI: 10.1186/1471-2105-13-55. View

Neuwald A . Surveying the manifold divergence of an entire protein class for statistical clues to underlying biochemical mechanisms. Stat Appl Genet Mol Biol. 2012; 10:Article 36. PMC: 3176138. DOI: 10.2202/1544-6115.1666. View

Lichtarge O, Bourne H, Cohen F . An evolutionary trace method defines binding surfaces common to protein families. J Mol Biol. 1996; 257(2):342-58. DOI: 10.1006/jmbi.1996.0167. View

10.

Andersen G, Valente L, Pedersen L, Kinzy T, Nyborg J . Crystal structures of nucleotide exchange intermediates in the eEF1A-eEF1Balpha complex. Nat Struct Biol. 2001; 8(6):531-4. DOI: 10.1038/88598. View

11.

Mihalek I, Res I, Lichtarge O . A family of evolution-entropy hybrid methods for ranking protein residues by importance. J Mol Biol. 2004; 336(5):1265-82. DOI: 10.1016/j.jmb.2003.12.078. View

12.

Zhu Z, Karlin S . Clusters of charged residues in protein three-dimensional structures. Proc Natl Acad Sci U S A. 1996; 93(16):8350-5. PMC: 38674. DOI: 10.1073/pnas.93.16.8350. View

13.

Sankararaman S, Sjolander K . INTREPID--INformation-theoretic TREe traversal for Protein functional site IDentification. Bioinformatics. 2008; 24(21):2445-52. PMC: 2572704. DOI: 10.1093/bioinformatics/btn474. View